Elaborately engineering of lipid nanoparticle for targeting delivery of siRNA and suppressing acute liver injury  

作　　者：Qiu Wang Qikun Jiang Dan Li Zimeng Yang Lin Gao Fan Liu Chang Li Yao Feng Zhonggui He Cong Luo Jin Sun 

机构地区：[1]Department of Pharmaceutics,Wuya College of Innovation,Shenyang Pharmaceutical University,Shenyang 110016,China [2]Kangya of Ningxia Pharmaceutical Co.Ltd.,Yinchuan 750000,China

出　　处：《Chinese Chemical Letters》2024年第2期323-328,共6页中国化学快报（英文版）

基　　金：financially supported by the National Key R&D Program of China(No.2021YFA0909900).

摘　　要：Small interfering RNA(siRNA)-based gene silencing has been considered as a potential therapy modality against inflammatory diseases.Nevertheless,the effective delivery of siRNA to desired destination still remains challenging due to poor stability,high molecular weight and negative charge.Currently,ionizable lipid nanoparticle(LNP)has been extensively used as vector for effective delivery of siRNA.Herein,we report a mannose-modified LNP(M-MC_(3) LNP@TNFα)loading tumor necrosis factorα(TNFα)siRNA for targeting liver macrophages,achieving effectively inhibit acute liver injury.The M-MC_(3) LNP@TNFαnot only increases the internalization of LNP by macrophages,but also enhances the gene silencing efficiency of TNFαin vitro.Additionally,the M-MC_(3) LNP@TNFαexhibits higher accumulation in liver of healthy mice than that of MC_(3) LNP@TNFα(un-modified LNP)owing to the targeting effect of mannose.As expected,the M-MC_(3) LNP@TNFαsignificantly suppresses the expression of TNFαand ameliorates liver damage in acute liver injury model.Such a LNP targeting siRNA delivery holds great potential for the treatment of diseases associated with liver in the future.

关 键 词：Lipid nanoparticle Targeting siRNA delivery Acute liver injury Gene silencing Tumor necrosis factorα 

分 类 号：TB383.1[一般工业技术—材料科学与工程] R575[医药卫生—消化系统]